Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Int J Radiat Oncol Biol Phys. 2017 Feb 1;97(2):323-332. doi: 10.1016/j.ijrobp.2016.10.046. Epub 2016 Nov 8.
To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC).
177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gy (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors.
The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20 (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia.
Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.
确定在接受局部晚期胰腺癌（LAPC）根治性放化疗（CRT）的患者中，无意照射的脾脏的淋巴细胞减少的严重程度是否取决于辐射剂量和分数体积。
177 例 LAPC 患者于 2006 年 1 月至 2012 年 12 月接受诱导化疗（主要为吉西他滨为基础的方案），随后进行 CRT（中位数 50.4Gy，同时给予卡培他滨）。在基线、CRT 前和 CRT 后 2 至 10 周记录绝对淋巴细胞计数（ALC）。脾剂量-体积直方图（DVH）参数以平均脾剂量（MSD）和脾体积接受至少 5-（V5）、10-（V10）、15-（V15）和 20-Gy（V20）剂量的百分比报告。使用 Cox 模型分析总生存期（OS），使用基线和治疗因素的多变量逻辑回归评估 CRT 后严重淋巴细胞减少（ALC <0.5K/UL）的发生情况。
CRT 后中位 ALC（0.68K/UL；范围，0.13-2.72）明显低于基线 ALC（1.42K/UL；范围，0.34-3.97；P<.0001）和 CRT 前 ALC（1.32K/UL，范围 0.36-4.82；P<.0001）。单因素分析显示，CRT 后 ALC <0.5K/UL 与较差的 OS 相关（中位值，11.1 与 15.3 个月；P=.01），多因素分析也显示（风险比=1.66，P=.01）。MSD（9.8 与 6Gy，P=.03）、中位 V10（32.6 与 16%，P=.04）、V15（23.2 与 9.5%，P=.03）和 V20（15.4 与 4.6%，P=.02）在严重淋巴细胞减少患者中明显高于无严重淋巴细胞减少患者。多因素分析显示，诱导后淋巴细胞减少（P<.001；优势比[OR] =5.25）和 MSD（P=.002；OR=3.42）是严重 CRT 后淋巴细胞减少发生的独立预测因素。
严重的 CRT 后淋巴细胞减少是接受 CRT 的 LAPC 患者预后不良的独立预测因素。较高的脾脏剂量会增加发生严重 CRT 后淋巴细胞减少的风险。在临床需要时，在接受治疗计划之前评估脾脏 DVH 可以最大限度地降低严重 CRT 后淋巴细胞减少的风险。
